Zanamivir Oral Delivery: Enhanced Plasma and Lung Bioavailability in Rats.
- Author:
Srinivasan SHANMUGAM
1
;
Ho Taek IM
;
Young Taek SOHN
;
Kyung Soo KIM
;
Yong Il KIM
;
Chul Soon YONG
;
Jong Oh KIM
;
Han Gon CHOI
;
Jong Soo WOO
Author Information
1. Pharm. R&D Institute, Hanmi Pharm. Co., Ltd., Hwasung 445-913, Republic of Korea. jswoo@hanmi.co.kr
- Publication Type:Original Article
- Keywords:
Zanamivir oral delivery;
Permeation enhancer;
Bioavailability enhancement;
Sodium caprate;
Influenza
- MeSH:
Administration, Oral;
Animals;
Biological Availability*;
Caco-2 Cells;
Humans;
Influenza, Human;
Inhibitory Concentration 50;
Lung*;
Orthomyxoviridae;
Permeability;
Plasma*;
Rats*;
Sodium;
Sodium Cholate;
Zanamivir*
- From:Biomolecules & Therapeutics
2013;21(2):161-169
- CountryRepublic of Korea
- Language:English
-
Abstract:
The objective of this study was to enhance the oral bioavailability (BA) of zanamivir (ZMR) by increasing its intestinal permeability using permeation enhancers (PE). Four different classes of PEs (Labrasol(R), sodium cholate, sodium caprate, hydroxypropyl beta-cyclodextrin) were investigated for their ability to enhance the permeation of ZMR across Caco-2 cell monolayers. The flux and Papp of ZMR in the presence of sodium caprate (SC) was significantly higher than other PEs in comparison to control, and was selected for further investigation. All concentrations of SC (10-200 mM) demonstrated enhanced flux of ZMR in comparison to control. The highest flux (13 folds higher than control) was achieved for the formulation with highest SC concentration (200 mM). The relative BA of ZMR formulation containing SC (PO-SC) in plasma at a dose of 10 mg/kg following oral administration in rats was 317.65% in comparison to control formulation (PO-C). Besides, the AUC0-24 h of ZMR in the lungs following oral administration of PO-SC was 125.22 +/- 27.25 ng hr ml(-1) with a Cmax of 156.00 +/- 24.00 ng/ml reached at 0.50+/-0.00 h. But, there was no ZMR detected in the lungs following administration of control formulation (PO-C). The findings of this study indicated that the oral formulation PO-SC containing ZMR and SC was able to enhance the BA of ZMR in plasma to an appropriate amount that would make ZMR available in lungs at a concentration higher (>10 ng/ml) than the IC50 concentration of influenza virus (0.64-7.9 ng/ml) to exert its therapeutic effect.
